Glycosaminoglycans such as chondroitin sulfate (CS) play a critical role in various physiological processes, including cell division, inflammation, and spinal cord injury. However, the complexity of this class of natural molecules has made correlating structure to function difficult. Furthermore, it has not been retrieval to generate glycosaminoglycan with controllable sulfation pattern.
Comprising 40-200 sulfated disaccharide units, CS is thought to contain “blocks” of high and low sulfation, with highly sulfated regions serving as binding sites for growth factors, cytokines, and other proteins. Although a tetrasaccharide can be sufficient for molecular recognition and neuronal activity, longer sequences are thought to be useful for enhancing protein binding and allowing for the assembly of multimeric protein complexes.
Thus far very few polymers based on glycosaminoglycan structures have been reported. Heparin-like glycopolymers have been synthesized from simple monosaccharides such as N-acetyl-D-glucosamine. However, no high molecular weight glycopolymers have been assembled from disaccharide building blocks found in heparin/heparan sulfate, chondroitin, dermatan, or keratan sulfate glycosaminoglycans. Such glycopolymers would more closely mimic the natural polysaccharides, and hence facilitating explorations into the importance of macromolecular structure (e.g., distance, number, and orientation between protein-binding epitopes, multivalency).